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Biomedical subjects

R E Baughn

Publications and source records attributed to R E Baughn.

At least 19 recordsLinked to original sources
PubMed2001

Nonspecificity of assaying for IgG antibody to pneumolysin in circulating immune complexes as a means to diagnose pneumococcal pneumonia.

Detection of immunoglobulin G (IgG) antibody to pneumolysin (PLY) in precipitated circulating immune complexes (CICs) has been used to diagnose pneumococcal pneumonia. With care to include appropriate controls, we precipitated and dissociated CICs and then assayed for IgG antibody to PLY. We detected IgG antibody to PLY in CICs that were precipitated from serum samples that were obtained at the time of admission to the hospital from 5 (23%) of 22 healthy adults, 7 (44%) of 16 subjects with stable chronic obstructive pulmonary disease, 10 (63%) of 16 subjects colonized with Streptococcus pneumoniae, and 9 (60%) of 15 patients with nonbacteremic pneumococcal pneumonia. Of the 16 patients with bacteremic pneumococcal pneumonia, 4 (25%) had IgG antibody to PLY at the time of admission, and 8 (50%) had IgG antibody to PLY in convalescence. Levels of IgG antibody in CICs closely correlated with serum levels of IgG antibody to PLY, implicating precipitation of free serum antibody in tests with false-positive results. Detection of IgG antibody to PLY in precipitated CICs is not a reliable method for diagnosing pneumococcal pneumonia.

Adult↗
PubMed2001

Protection against bacteremic pneumococcal infection by antibody to pneumolysin.

Pneumolysin is an important virulence factor of Streptococcus pneumoniae. This study examined the hypothesis that human antibody to pneumolysin provides protection against pneumococcal infection. At the time of hospital admission, patients with nonbacteremic pneumococcal pneumonia had higher levels of serum anti-pneumolysin IgG than did patients with bacteremic pneumococcal pneumonia or uninfected control subjects. IgG levels rose significantly during convalescence in patients with bacteremic pneumonia, reaching levels observed in nonbacteremic patients. Purified human anti-pneumolysin IgG protected mice against intraperitoneal challenge with S. pneumoniae types 1 or 4 in a dose-related fashion; mice that received anti-pneumolysin IgG had a greater likelihood of surviving challenge and had negative blood cultures. Pneumolysin damages epithelial cells and inhibits phagocytic function of polymorphonuclear leukocytes. One hypothesis that might explain the study results is that, early in infection, IgG to pneumolysin blocks these effects in the alveoli, thereby protecting the host against bacteremic pneumococcal disease.

Animals↗
PubMed2000

A novel membrane-anchored Rab5 interacting protein required for homotypic endosome fusion.

The ras-related GTPase rab5 is rate-limiting for homotypic early endosome fusion. We used a yeast two-hybrid screen to identify a rab5 interacting protein, rab5ip. The cDNA sequence encodes a ubiquitous 75-kDa protein with an N-terminal transmembrane domain (TM), a central coiled-coil structure, and a C-terminal region homologous to several centrosome-associated proteins. rab5ip lacking the transmembrane domain (rab5ipTM(-)) had a greater affinity in vitro for rab5-guanosine 5'-O-2-(thio)diphosphate than for rab5-guanosine 5'-3-O-(thio)triphosphate. In transfected HeLa cells, rab5ipTM(-) was partly cytosolic and localized (by immunofluorescence) with a rab5 mutant believed to be in a GDP conformation (GFP-rab5(G78A)) but not with GFP-rab5(Q79L), a GTPase-deficient mutant. rab5ip with the transmembrane domain (rab5ipTM(+)) was completely associated with the particulate fraction and localized extensively with GFP-rab5(wt) in punctate endosome-like structures. Overexpression of rab5ipTM(+) using Sindbis virus stimulated the accumulation of fluid-phase horseradish peroxidase by BHK-21 cells, and homotypic endosome fusion in vitro was inhibited by antibody against rab5ip. rab5ipTM(-) inhibited rab5(wt)-stimulated endosome fusion but did not inhibit fusion stimulated by rab5(Q79L). rab5ip represents a novel rab5 interacting protein that may function on endocytic vesicles as a receptor for rab5-GDP and participate in the activation of rab5.

Amino Acid Sequence↗
PubMed2000

Antibody to capsular polysaccharide of Streptococcus pneumoniae at the time of hospital admission for Pneumococcal pneumonia.

IgG to capsular polysaccharide (CPS) of Streptococcus pneumoniae is thought to provide the greatest degree of protection against pneumococcal disease. Serum obtained at hospital admission from 14 (27%) of 51 patients with bacteremic pneumococcal pneumonia and 11 (37%) of 30 with nonbacteremic pneumococcal pneumonia contained IgG to CPS of the infecting serotype; these percentages are similar to the prevalence of IgG to CPS in a control population. However, when compared with antibody from healthy adults, this IgG had far less capacity to opsonize the infecting pneumococcal serotype for phagocytosis in vitro by normal human polymorphonuclear leukocytes or to protect mice against experimental challenge. Failure to opsonize correlated closely with failure to protect mice, and each of these parameters correlated well with poor avidity for CPS. Future vaccine studies may need to examine the functional capacity of antibodies as a surrogate for infection, in addition to measuring their concentration in serum.

Animals↗
PubMed2000

Treponema pallidum subsp. pertenue displays pathogenic properties different from those of T. pallidum subsp. pallidum.

The present study described the susceptibility of C4D guinea pigs to cutaneous infection with Treponema pallidum subsp. pertenue Haiti B strain. The general manifestations of the disease in adults and neonates differ, to a certain degree, from those induced by T. pallidum subsp. pallidum Nichols strain. Noticeable differences between the infections were reflected in the character of the skin lesions, their onset and persistence, and the kinetics of the humoral response. The incidence and dissemination of cutaneous yaws lesions in very young guinea pigs were remarkably different from the low frequency observed in a similar age group of syphilis infection, 100 versus 17%, respectively. Moreover, as opposed to T. pallidum subsp. pallidum, T. pallidum subsp. pertenue does not cross the placenta. Offspring born to yaws-infected mothers did not produce immunoglobulin M antibodies and their organs, examined by PCR and rabbit infectivity test (RIT), were all negative. Examination of a large number of tissues and organs in adult, neonate, and maternal yaws by PCR and RIT clearly demonstrated that, unlike syphilis, there was a low incidence and short persistence of the yaws pathogen in internal organs. These findings stress the dermotropic rather than the organotropic character of yaws and provide further evidence of distinctive biological and pathological differences between yaws and venereal syphilis.

Age Factors↗
PubMed2000

Whole-blood hemagglutination inhibition test for venereal disease research laboratory (VDRL) antibodies.

Nontreponemal antibody tests such as the Venereal Disease Research Laboratory (VDRL) test are carried out on serum and widely used as screening tests for syphilis. The aim of the present study was to develop a screening test for syphilis making use of whole blood and VDRL liposomes. Antibody to human red blood cells was conjugated to VDRL liposomes and reacted with a diluted sample of patient whole blood. A total of 951 samples were tested by the new test and the VDRL tube test. All 49 VDRL samples positive by the VDRL test showed inhibition of hemagglutination in the whole-blood test (sensitivity, 100%). Of 902 samples with negative results by the VDRL test, 901 caused hemagglutination when tested with the liposomes (specificity, 99.9%). The hemagglutination inhibition method tests for syphilis in a simple one-step procedure in which whole blood is added to a tube containing liposomes. The new test has potential for point-of-care testing in developing countries.

Animals↗
PubMed1999

Vertical transmission of Treponema pallidum to various litters and generations of guinea pigs.

The transmission of congenital syphilis was studied in a 4-generation guinea pig family with 10 litters and 38 offspring. By use of one or all of the following tests (ELISA-IgM, polymerase chain reaction, and rabbit infectivity), transplacental infection was demonstrated through 5 litters and up to 4 generations. Twenty-eight (93%) of 30 animals were positive by >/=1 test, and 2 (7%) were negative by 1 or 3 tests. While transmission of the pathogen appeared to be unaffected by the maternal acquisition of immunity, signs of smoldering infection in the young was suggested by the decline in humoral responses in successive progeny and by unusual rabbit infectivity test results. With each pregnancy there was a remarkable booster in the maternal humoral response, which dropped significantly prior to term. These findings shed new light on the understanding and interpretation of serologic testing during pregnancy and the perinatal period.

Animals↗
PubMed1999

Fibronectin fragments modulate monocyte VLA-5 expression and monocyte migration.

To identify the mechanisms that cause monocyte localization in infarcted myocardium, we studied the impact of ischemia-reperfusion injury on the surface expression and function of the monocyte fibronectin (FN) receptor VLA-5 (alpha(5)beta(1) integrin, CD49e/CD29). Myocardial infarction was associated with the release of FN fragments into cardiac extracellular fluids. Incubating monocytes with postreperfusion cardiac lymph that contained these FN fragments selectively reduced expression of VLA-5, an effect suppressed by specific immunoadsorption of the fragments. Treating monocytes with purified, 120-kDa cell-binding FN fragments (FN120) likewise decreased VLA-5 expression, and did so by inducing a serine proteinase-dependent proteolysis of this beta(1) integrin. We postulated that changes in VLA-5 expression, which were induced by interactions with cell-binding FN fragments, may alter monocyte migration into tissue FN, a prominent component of the cardiac extracellular matrix. Support for this hypothesis came from experiments showing that FN120 treatment significantly reduced both spontaneous and MCP-1-induced monocyte migration on an FN-impregnated collagen matrix. In vivo, it is likely that contact with cell-binding FN fragments also modulates VLA-5/FN adhesive interactions, and this causes monocytes to accumulate at sites where the fragment concentration is sufficient to ensure proteolytic degradation of VLA-5.

Amino Acid Sequence↗
PubMed1998

IgG responses to protein-conjugated pneumococcal capsular polysaccharides in persons who are genetically incapable of responding to unconjugated polysaccharides.

We have previously shown that the capacity to make IgG to pneumococcal capsular polysaccharides (PCPs) is inherited as an autosomal, mixed codominant trait. The purpose of this study was to determine whether this genetically determined unresponsiveness could be overcome by injection of protein-conjugated pneumococcal vaccines. Seven healthy adults who had failed to produce IgG to five or more of 10 representative PCPs after receiving pneumococcal vaccine and whose parents, siblings, and/or offspring had a similar lack of responsiveness received a series of protein-conjugated polysaccharide vaccines. Excellent IgG responses to most of the PCPs tested were eventually observed in five of the seven subjects after they received octavalent diphtheria toxoid-conjugated vaccine. Administration of certain protein-conjugated PCPs leads to IgG responses in some persons who lack the capacity to respond to unconjugated PCPs.

Adult↗
PubMed1997

Emergence of antibody to capsular polysaccharides of Streptococcus pneumoniae during outbreaks of pneumonia: association with nasopharyngeal colonization.

Antibody to pneumococcal capsular polysaccharides (PPS) of Streptococcus pneumoniae plays a major role in protecting the host against pneumococcal infection. A variable proportion of healthy adults have antibody to PPS, often in the absence of recognized pneumococcal infection. To determine whether exposure to pneumococci or colonization by pneumococci, or both, stimulates the emergence of antibody to PPS, we studied outbreaks of pneumonia at two military camps. Of the men who were present at a military training camp during an outbreak of pneumonia due to S. pneumoniae serotype 1 but who did not develop pneumonia, 27.8% had IgG antibody to PPS 1, whereas only 3.6% of controls had this antibody. In another outbreak caused by S. pneumoniae serotypes 7F and 8, 35.9% of asymptomatic soldiers who had nasopharyngeal colonization by one of these strains had antibody to the relevant PPS, and another 30.8% who originally did not have antibody developed it within 30 days; thus, 66.7% of these soldiers had antibody to the relevant PPS. These data show that serotype-specific antibody promptly appears following exposure to an outbreak of pneumococcal pneumonia and is probably mediated through acquisition of nasopharyngeal pneumococcal carriage.

Adult↗
PubMed1997

Genetic regulation of the capacity to make immunoglobulin G to pneumococcal capsular polysaccharides.

BACKGROUND: Genetic regulation of immunoglobulin G(IgG) responses to pneumococcal capsular polysaccharides (PPS), has been demonstrated in mice but not in humans. Earlier studies from this laboratory showed that healthy adults have a varying capacity to generate IgG antibody to PPS; this study sought to determine whether this capacity is genetically controlled. METHODS: A 23-valent pneumococcal vaccine was administered to 72 unrelated White adults, 4 nuclear families, and 61 members of an extended Ashkenazic Jewish family. Selected individuals later received one or more doses of the vaccine and/or a single dose of protein-conjugated PPS. Four to six weeks after each vaccination, IgG to PPS was measured by ELISA. Immunoglobulin allotypes and HLA types were determined by standard techniques. RESULTS: After vaccination, 53% of the 72 unrelated White adults had measurable levels of IgG antibody to all of 10 PPS studied (high-level responders), 36% had IgG to 6-9 PPS, and 11% had IgG to < or = 5 of 10 PPS (low-level responders). Persons who did not make IgG to an individual PPS also failed to make IgM or IgA to that antigen. Low-level responders had reduced mean IgG levels to PPS to which they did make IgG; nevertheless, their total serum concentrations of IgG, IgG2, IgA, and IgM were normal, and each made IgG2 to at least one PPS, all indicating that a global defect in Ig production was not responsible. The responder status of offspring was highly associated with that of their parents. Segregation analysis of 61 Ashkenazic family members revealed that the capacity to generate anti-PPS IgG was inherited in a mixed, codominant fashion. Repeated vaccination or administration of protein-conjugated PPS did not elicit measurable IgG in nonresponders. The HLA type was not associated with antibody responses. An association between IgG level and Gm(23)+ allotype was observed in unrelated Whites but not in Ashkenazic Jews. CONCLUSIONS: Thus, humans exhibit a variable capacity to respond to PPS. This response is hereditable in a mixed, codominant fashion. The absence of IgG to a PPS, even after antigen is presented in a protein-conjugate form, may reflect a genetically mediated failure to recognize polysaccharide antigens. Since persons who respond to fewer PPS also have lower levels of IgG to PPS to which they do respond, genetically determined deficiencies in events that involve proliferation of committed B lymphocytes may also play a role.

Adolescent↗
PubMed1996

Molecular mimicry between an immunodominant amino acid motif on the 47-kDa lipoprotein of Treponema pallidum (Tpp47) and multiple repeats of analogous sequences in fibronectin.

Molecular mimicry, resulting from structural similarities between self-determinants on host Ags and an organism's antigenic determinants (epitopes), can incite autoimmune events in certain bacterial and viral diseases. In the course of comprehensively mapping the 47-kDa lipoprotein (Tpp47) of Treponema pallidum subsp. pallidum using an overlapping synthetic peptide strategy, we identified a major immunoreactive epitope (411PGTEYT416) that exhibited considerable motif identity with multiple repeats of analogous linear sequences found in mammalian fibronectins. To further explore the importance of this motif as a probable instigator in the induction of polyspecific cross-reactive Abs, mimetic variants were synthesized for immunologic studies. Mimetics with ala (A) replacements in each amino acid position were used to determine which residues were critical for Ab binding. Animals immunized with two mimetics (PGTEYT or PGSEYT) coupled to tetanus toxoid exhibited: 1) modified responses when challenged with viable T. pallidum; and 2) classical Arthus reactions when challenged intradermally with either motif linked to a different carrier. The cross-reactive nature of the Ab responses to both mimetics was confirmed in a variety of ELISAs using mimetics, fibronectins, and collagens. Inhibition-ELISA studies with both fibronectin and an unrelated mimetic of the RGD motif suggest that intra- and intermolecular epitope spreading occurs following mimetic immunization and involves additional self-epitopes. These observations suggest that although molecular mimicry plays a pivotal role in initially triggering the anti-fibronectin and anti-collagen responses associated with disseminated syphilis, expansion of those autoimmune responses may be due to other self-epitopes once tolerance is abrogated.

Amino Acid Sequence↗
PubMed1996

The lack of association between aging and postvaccination levels of IgG antibody to capsular polysaccharides of Streptococcus pneumoniae.

One possible explanation for the apparently reduced efficacy of pneumococcal vaccine in elderly subjects is that IgG responses to pneumococcal capsular polysaccharides (PPSs) decline with aging. We administered pneumococcal vaccine to 118 adults who ranged in age from 20 to 93 years; 33 were > or = 70 years old. Four to 6 weeks later, we measured IgG reactive with PPSs from 10 commonly infecting serotypes of Streptococcus pneumoniae. By regression analysis, a slight but nonsignificant increase in anti-PPS IgG was observed with increased age for six serotypes and a nonsignificant decrease was observed for four. Mean IgG levels and the percentage of subjects with IgG levels > or = 1 microgram/mL were no different among persons > or = 70 years of age than among those < or = 69 years of age. These results show no consistent effect of aging on anti-PPS IgG levels 4-6 weeks after pneumococcal vaccination.

Adult↗
PubMed1996

Epitope mapping of B-cell determinants on the 15-kilodalton lipoprotein of Treponema pallidum (Tpp15) with synthetic peptides.

The antigenicity of the 15-kDa lipoprotein of Treponema pallidum (Tpp15 or TpN15) was comprehensively evaluated in epitope-scanning studies with overlapping deca- and octapeptides and polygonal rabbit and human infant immunoglobulins (Igs) and antisera. This approach enabled us to identify potentially important regions and to determine the optimal dilutions of Igs or antisera for use in further studies. IgM and IgG from both species were capable of recognizing multiple, continuous epitopes. A total of 13 peptides, principally clustered in the central regions of the protein, were recognized by all syphilitic sera and Ig fractions. On the basis of window analyses, frequency profiles, and alanine substitution studies, five heptapeptides were selected for mimetic studies. Two of these five immunodominant, continuous epitopes initially appeared to be species specific; however, antisera elicited against mimetics of all five epitopes were polyspecific, recognizing similar motifs on several other treponemal proteins, including those of avirulent organisms. The only mimetic which yielded positive reactions with infant IgM and syphilitic sera in the absence of cross-reactions with rabbit antisera to avirulent treponemes was the variant of the VMYASSG motif. These findings are relevant to the development of simple, inexpensive assays for the serodiagnosis of active syphilis.

Amino Acid Sequence↗
PubMed1995

In vitro evaluation of the role of humoral immunity against Bartonella henselae.

The contribution of humoral immunity against Bartonella henselae was evaluated by examining the in vitro bactericidal activity of sera and the ability of these microorganisms to activate complement and stimulate phagocytosis and an oxidative burst in polymorphonuclear leukocytes. The organism was killed by complement-mediated cytolysis. Complement activation preferentially proceeded by the alternative pathway. The presence of specific antibodies did not increase the serum bactericidal activity or complement activation. However, phagocytosis and the subsequent production of oxygen radicals, evaluated by flow cytometry, were significantly enhanced in the presence of bacteria previously opsonized with immune sera.

Adult↗
PubMed1994

Analysis of western blotting (immunoblotting) technique in diagnosis of congenital syphilis.

The diagnosis of congenital syphilis in apparently healthy infants continues to be problematic. Immunoglobulin M antibodies specific for a subset of Treponema pallidum antigens have been detected by Western blotting (immunoblotting). In the present study we investigated the sensitivity and specificity of this method. We tested 26 infants aged 0 to 4 months who fulfilled the accepted criteria for the diagnosis of congenital syphilis. There were 14 symptomatic infants. Sera from 13 of these infants were positive for the 47-kDa treponemal antigen (92% sensitivity). The remaining 12 infants were clinically asymptomatic when tested at birth but subsequently displayed features consistent with the disease. Reactive blots (antibodies to the 47- and/or the 15-kDa antigens) were noted in 10 of the 12 infants (83% sensitivity). Thirty infants whose mothers had syphilis were monitored and shown to be uninfected. Nonreactive blots were seen in sera from 27 infants, while sera from 3 older infants had false-positive tests (90% specificity). The Western blotting technique is sensitive (even in the diagnosis of clinically inapparent cases) and, in the absence of immunoglobulin M rheumatoid factor, is a useful confirmatory test for congenital syphilis.

Antibodies, Bacterial↗